Regulation of the thiamine pyrophosphate (TPP)-sensing riboswitch in NMT1 mRNA from Neurospora crassa

Abstract

The expression of Neurospora crassa NMT1 involved in thiamine pyrophosphate (TPP) metabolism is regulated at the level of mRNA splicing by a TPP-sensing riboswitch within the precursor NMT1 mRNA. Here, using the systematic helix-based computational method, we investigated the regulation of this riboswitch. We find that the function of the riboswitch does not depend on the transcription process. Whether TPP is present or not, the riboswitch predominately folds into the ON state, while the OFF state aptamer structure does not appear during transcription. Since the transition from the ON state to the aptamer structure is extremely slow, TPP may interact with the RNA before full formation of the aptamer structure, promoting the switch flipping. The potential to fully form helix P0 of the ON state is necessary to restore ligand-dependent gene control by the riboswitch.